Upregulation of tissue factor expression and thrombogenic activity in human aortic smooth muscle cells by irradiation, rapamycin and paclitaxel

International Immunopharmacology
Andreas EisenreichUrsula Rauch

Abstract

Intracoronary brachytherapy as well as rapamycin or paclitaxel coated stents reduce restenosis rates after stenting, but are associated with an increased risk of late stent thrombosis. Tissue factor (TF) may contribute to late thrombosis. This study examined the impact of rapamycin and paclitaxel on TF expression and compares the TF activity induction of both drugs and irradiation in SMCs. SMCs were stimulated with rapamycin, paclitaxel or irradiation. Real-time PCR, a chromogenic TF activity assay and Western blotting were done. Rapamycin or paclitaxel increased the TF mRNA expression 5-fold and the TF activity 4- to 6-fold with a maximum at 5 h. Irradiation induced TF activity 2- to 4-fold with a maximum at 7 days. The fast increase of TF expression in SMCs post rapamycin and paclitaxel treatment may explain acute stent thrombosis when anti-thrombotic therapies are withdrawn, whereas the irradiation induced long term increase of cellular thrombogenicity may contribute to late thrombosis post intracoronary brachytherapy. Therapies counteracting these side effects may reduce the risk of thrombotic complications after the coronary application of anti-proliferative therapies.

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Citations

Sep 14, 2010·American Journal of Respiratory and Critical Care Medicine·Sangeeta BhoradeEdward Garrity
Mar 11, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Andreas EisenreichUrsula Rauch
Jul 15, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Andreas EisenreichUrsula Rauch
Nov 30, 2013·Thrombosis·Andreas Eisenreich
May 9, 2014·International Journal of Cancer. Journal International Du Cancer·Ulrike Leppert, Andreas Eisenreich
Oct 15, 2013·Trends in Cardiovascular Medicine·Andreas Eisenreich, Ulrike Leppert
Jan 17, 2014·Kidney International·Jacobien C VerhaveHéloïse Cardinal
Aug 1, 2010·Trends in Cardiovascular Medicine·Andreas Eisenreich, Ursula Rauch
Jan 19, 2011·Cardiovascular Revascularization Medicine : Including Molecular Interventions·Yunus AyralKlaus Pels
Jul 11, 2012·Clinical Transplantation·Jennifer T ThibodeauMark H Drazner
Jul 16, 2010·Cardiovascular Therapeutics·Andreas Eisenreich, Ursula Rauch
Dec 3, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Emanuela NapoleoneRoberto Lorenzet
Nov 11, 2008·International Immunopharmacology·Huang-Joe WangHuey-Chun Huang
Jan 16, 2010·Journal of Cardiovascular Pharmacology·Steven C WoodBelay Tesfamariam
Mar 15, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Lee S NguyenJoe-Elie Salem

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